Abstract
BackgroundAdenomyosis is a chronic gynecological disease characterized by invasion of the uterine endometrium into the muscle layer. In assisted reproductive technology (ART), gonadotropin-releasing hormone agonist (GnRHa) is often used to improve pregnancy rates in patients with adenomyosis, but the underlying mechanisms are poorly understood.MethodsEutopic endometrial specimens were collected from patients with adenomyosis before and after GnRHa treatment in the midsecretory phase. RNA sequencing (RNA-Seq) of these specimens was performed for transcriptome analysis. The differentially expressed genes (DEGs) of interest were confirmed by real-time PCR and immunohistochemistry.ResultsA total of 132 DEGs were identified in the endometrium of patients with adenomyosis after GnRHa treatment compared with the control group. Bioinformatics analysis predicted that immune system-associated signal transduction changed significantly after GnRHa treatment. Chemokine (C-C motif) ligand 21 (CCL21) was found to be highly expressed in the eutopic endometrium after GnRHa treatment, which may be involved in the improvement of endometrial receptivity in adenomyosis.ConclusionThis study suggests that molecular regulation related to immune system-associated signal transduction is an important mechanism of GnRHa treatment in adenomyosis. Immunoreactive CCL21 is thought to regulate inflammatory events and participate in endometrial receptivity in adenomyosis.
Highlights
Adenomyosis is a chronic gynecological disease characterized by invasion of the uterine endometrium into the muscle layer
RNA‐Seq analysis and identification of differentially expressed genes (DEGs) To better understand the effect of gonadotropin-releasing hormone agonist (GnRHa) in adenomyotic endometrial tissue, we conducted a comparative transcriptomic analysis of the endometrium in 9 patients before and after GnRHa treatment
Among the identified DEGs mentioned above, 81 genes were upregulated, and 51 genes were downregulated in eutopic endometrium from patients with adenomyosis compared to that from the control subjects
Summary
Adenomyosis is a chronic gynecological disease characterized by invasion of the uterine endometrium into the muscle layer. In assisted reproductive technology (ART), gonadotropin-releasing hormone agonist (GnRHa) is often used to improve pregnancy rates in patients with adenomyosis, but the underlying mechanisms are poorly understood. Adenomyosis is defined by the presence of endometrial glands and stroma within the myometrium and diffuse enlargement of the uterus. It preferentially affects parous women between the ages of 35 and 50 years, Tian et al Reproductive Biology and Endocrinology (2022) 20:13 patients [4, 5]. GnRHa treatment is associated with a dramatic improvement in clinical pregnancy rates in adenomyosis patients with recurrent implantation failure (RIF) [6]. Elucidating the systemic role and underlying cellular regulatory mechanisms of GnRHa treatment in adenomyosis is necessary to identify impaired endometrial receptivity in adenomyosis-associated infertility
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